Multiple lines of evidence support the viral and the immunologic hypotheses in Multiple Sclerosis (MS). However, no one virus has been reproducibly isolated from MS patients, and the specificity of antibody produced within the CNS in MS is undefined. Although soluble immune complexes (ICx) have been detected in low concentration in CSF of patients with MS, the antigen moiety in these complexes is unknown. The antigen component must be of either exogenous or endogenous origin. Characterization ICx components might implicate exogenous factors (e.g. virus) or endogenous antigens in pathogenesis of MS. Quanlities of ICx available in CSF from MS patients are insufficient for traditional biochemical approaches to antigen characterization, and immunochemical approaches require a prior notion as to the nature of the antigen present. To circumvent these problems, we have developed an approach to ICx characterization that is both sensitive and direct. We propose to apply this method to the study of ICx in CSF of MS patients. We have shown that anti-IgG conjugated to ferritin (anti-IgG-F) can be used to separate soluble ICx from solution, even in the presence of a 200-fold excess of monomeric IgG. Further, we have utilized anti-IgG-F to isolate model ICx on a sucrose density gradient and to simultaneously label model ICx with ferritin, a distinctive EM marker. We have used negative stain EM preparative techniques for high resolution ultrastructural study of the immunologically labeled, isolated model ICx. This simple and direct technique will be applied to the ICx of patients with MS and other neurologic diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000791-04
Application #
3078146
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1983-04-01
Project End
1986-12-31
Budget Start
1986-04-01
Budget End
1986-12-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Rudick, R A; Schiffer, R B; Schwetz, K M et al. (1986) Multiple sclerosis. The problem of incorrect diagnosis. Arch Neurol 43:578-83
Rudick, R A; Jacobs, L; Kinkel, P R et al. (1986) Isolated idiopathic optic neuritis. Analysis of free kappa-light chains in cerebrospinal fluid and correlation with nuclear magnetic resonance findings. Arch Neurol 43:456-8
Rudick, R A; Pallant, A; Bidlack, J M et al. (1986) Free kappa light chains in multiple sclerosis spinal fluid. Ann Neurol 20:63-9
Birk, K; Rudick, R (1986) Pregnancy and multiple sclerosis. Arch Neurol 43:719-26
Knutson, D W; Rudick, R A; Herndon, R M (1985) Isolation of model soluble immune complexes in the fluid phase by monoclonal anti-IgG-ferritin antibodies. Scand J Immunol 21:1-9
Rudick, R A; Bidlack, J M; Knutson, D W (1985) Multiple sclerosis. Cerebrospinal fluid immune complexes that bind C1q. Arch Neurol 42:856-8
Rudick, R A; Peter, D R; Bidlack, J M et al. (1985) Multiple sclerosis: free light chains in cerebrospinal fluid. Neurology 35:1443-9